KLRG1

Chr 12

killer cell lectin like receptor G1

Also known as: 2F1, CLEC15A, MAFA, MAFA-2F1, MAFA-L, MAFA-LIKE

NCBI Gene: 10219ENSG00000139187UniProt: Q96E93

The KLRG1 protein is a killer cell lectin-like receptor that inhibits natural killer (NK) cell and T-cell functions by binding to classical cadherins including E-cadherin, serving as a "missing self" recognition mechanism for immune surveillance. This gene is not well-constrained against loss-of-function variants and no specific Mendelian diseases have been definitively associated with KLRG1 mutations in the current literature. Further research is needed to establish clear disease associations and inheritance patterns for this immune receptor gene.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
74
Pubs (1 yr)
22
P/LP submissions
0%
P/LP missense
1.18
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— KLRG1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 337 VUS of 500 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.003
Z-score 1.21
OE 0.56 (0.29–1.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.78Z-score
OE missense 0.77 (0.64–0.94)
73 obs / 94.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.29–1.18)
0≤0.351.4
Missense OE0.77 (0.64–0.94)
0≤0.61.4
Synonymous OE0.73
0≤1.21.6
LoF obs/exp: 5 / 8.9Missense obs/exp: 73 / 94.4Syn Z: 1.23
DN
0.87top 5%
GOF
0.75top 25%
LOF
0.11100th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS337
Likely Benign48
Benign21
20
Pathogenic
2
Likely Pathogenic
337
VUS
48
Likely Benign
21
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
2
0
2
VUS
0
330
7
0
337
Likely Benign
0
31
3
14
48
Benign
1
5
4
11
21
Total13663625428

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KLRG1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients